Now that ACTs appear to be failing

It is no longer news, at least to general practice doctors and community pharmacists that our cherished Artemisinin-based Combination Therapies (ACTs) appear to have begun to fail. Though no one has produced a clinical trial documenting the scale and nature of this development in Nigeria, products sourced from leading proprietary and generic brands have been reported by some health care providers to be ineffective in achieving total clearance of the malaria parasite from the bloodstream as they once did. These observations are in volumes too numerous to be completely discounted.

There are many possible reasons for these observations. The first culprit could be poor diagnosis by the clinician. Next are adulteration and the use of mono therapy; and then the one we fear the most – resistance by the protozoa.

Most of our antimalarial medications are sourced from India and China and if one should go by the recent USFDA’s concerns about the quality of medications from these two countries, we might have a lot to be worried about. A notable pharmaceutical company in India, for example, was fined $500 Million dollars by the US FDA in 2013 for seven felony counts related to data fabrication about the safety of the company’s products over the prior decade.

The question is, if the United States could experience such massive scale adulteration by a renowned company, what could be the case for Nigeria, where we are yet to publicly indict any foreign pharmaceutical company? However, we believe that NAFDAC is doing a lot to protect the interests of Nigerians by ensuring consistency in the quality of antimalarial medications in the market.

That said, let’s assume that this is not a case of adulteration but rather, of resistance, which could as well have been caused by adulteration. Let us now evaluate a scenario where the malaria parasite is developing resistance to our therapy.

In the event of resistance to ACTs

At present, malaria accounts for more deaths and morbidity in Nigeria than in any other country in the world. At least, a whopping 300,000 individuals die annually from malaria in Nigeria. That is about 34 individuals per hour.

Each year, Nigeria experiences more than a 100 million malaria episodes. What this means is that if, for any reason, we fail to not have a cure for malaria, in one year alone, we would be facing an epidemic of monumental proportions. It is therefore right that we endeavour to evaluate scenarios like this so that we can, at least, prepare. It should be borne in mind that there are countries where ACTs have been proven to have failed.

One important thing to note is that, unlike Ebola, we could be facing this alone. Again, if our experience with Ebola and available therapies are anything to go by, the picture is definitely not an exciting one; hence my decision not to shy away from this article, regardless of how gloomy things may appear.

As health care practitioners, our job includes preparing for such public health emergencies and from our training, the following are obvious indicators we could use to evaluate our preparedness for such a day:

The presence of a long term strategic commitment

Institutional mandate

Ongoing research and development projects

Public–private ownership of the development challenge

Essentially, we need to ask ourselves if there is a long term strategic commitment by anyone, public or private, in preparing for a day like this. Is there an institution whose mandate includes harbouring and managing such a commitment? Are there sufficient will and resources deployed in the form of research and development projects to reflect such commitments? If there are, do we have sufficient local engagement of the stakeholders – both private and public – in ensuring the feasibility of such endeavours?

Presence of a long term strategic commitment

A study of the Ebola scenario offers some interesting highlights, one of which is that there was a long term strategy for the virus disease. Somebody was worrying about what could happen and was doing something about it. ZMapp, for example, represented a wonderful demonstration of the power of effective partnerships between public research organisations and the private industry. For such partnerships to occur, there must have been strategic commitment.

At present, malaria receives massive funding from a wide diversity of donors. In 2012 alone, funding for malaria control peaked at US$ 2.5billion, representing more than a fivefold increase since 2004, when funding was less than US$ 400 million. At the center of these interventions, specifically for drug treatments, are the Artemisinin-based Combination Therapies (ACTs). ACTs are recommended as the first-line treatment of malaria caused by P. falciparum, the most dangerous of the Plasmodium parasites that infect humans. By 2012, 79 countries and territories had adopted ACTs as first-line treatmentfor P. falciparum malaria.

According to the 2013 WHO World Malaria Report, parasite resistance to artemisinins has now been detected in four countries of the Greater Mekong sub region: Cambodia, Myanmar, Thailand and Viet Nam. In Cambodia’s Pailin province, resistance has been found to both of the components of multiple ACTs; therefore, special provisions for directly observed therapy using a non artemisinin-based combination (atovaquone+proguanil) have been introduced.

One could say with confidence that there is a commitment to research and development of new antimalarials, but if we are to judge by recent occurrences, such commitments have not yielded a product yet.

Institutional mandates

Still on the Ebola scenario. A study of the efforts made by the US government to prepare for an Ebola Virus Disease situation shows a strong degree of long–term cohesive thrust between different organisations that include the National Institute of Health (NIH), Centres for Disease Control and Prevention (CDC), the United States Army Medical Research Institute of Infectious Diseases (USMRIID), the Canadian government and a host of private pharmaceutical firms.Apparently, each member of the partnering group had been preparing for a time like this and the outbreak was simply an opportunity to evaluate their degree of preparedness.

One could point out that the United States, in particular, had reasons to take the Ebola Virus Disease seriously – considering that there are no known cures for EVD and that Ebola virus constitutes a potential biological weapon. That said, should malaria not be of more concern to Nigeria at least – considering that we bear the largest global burden of the disease?

Going by the volume of funding dedicated to malaria control and the plethora of organisations involved in its disbursement, one could say that “yes, there is a long term strategic commitment. Institutions like Global Fund, World Bank, WHO, National Malaria Control Programme and the Ministry of Health, are the ones leading such interventions in Nigeria.

Ongoing research and development projects

This is one area that I am bit bothered about – not necessarily about the volume of the interventions but in their ownership. Preliminary investigations suggest that there is no ownership, at least in Nigeria, of the much needed research and development endeavours required to prepare for this eventuality – the failure of ACTs, a scenario that is quite predictable.

We all know that, in no distant time, we are going to have increased resistance to ACTs and that Nigeria bears the world’s largest global burden; yet it appears there are insufficient coordinated efforts in preparation for this eventuality. Some of the events seen in the management of the Ebola outbreak suggest that in situations of national emergencies like the one seen with the Ebola Virus Disease, it is possible that seemingly available therapies can be withheld on various grounds.

Ownership is very important. Yes, there are ongoing research and development efforts in finding malaria therapies which, by the way, are not as many as the level of R and D investment in HIV although malaria kills more people than HIV in Nigeria. The issue is that I do not think Nigeria owns these efforts; if it does, it would show in the level of funding dedicated to it.

The National Institute for Pharmaceutical Research and Development (NIPRD), in my opinion, should be leading such an effort. I know they are working on some antimalarial projects, yet the level of funding dedicated to such ventures is abysmal by any standard. Considering the magnitude of the scenario, it should be a national emergency and a malaria research and development tax could be justified if our government believes the problem is insufficiency of resources.

Public-Private ownership of the development challenge

As mentioned earlier, the Nigerian government, through appropriate parastatals, should be engaging other public and private organisations to ensure effectiveness and efficiency. These organisations could be national or international. The private sector, because of their profit motive, bring a certain level of efficiency in their operations and their partnerships as shown also with the USA management of the Ebola scenario are critical in the timely delivery of intervention.

In the Nigeria scenario, government intervention could provide the impetus for private pharmaceutical firms to invest some resources to finding new antimalarial medication.

Heading home for answers

One area I believe we should look closely at is combination therapies – that is, of combining our local indigenous herbs/extracts with known existing therapies. The ACTs were born in like fashion.